In the field of tissue engineering, degradable biomaterials usually serve as a scaffold to provide mechanical support and a matrix for the ingrowth of new tissue. As new tissue forms on the scaffold, the biomaterial degrades until it is entirely dissolved. The degradation products are eliminated through the body's natural pathways, such as metabolic processes.
One example of the use of such biomaterials is as a temporary bone replacement. It is often desired to replace or reconstruct all or a portion of a living bone, such as when a bone has been broken or has been resected as a result of a bone tumor. In these instances, the missing bone can be replaced with a mechanical device, such as a pin, plate or the like, or it can be replaced with an implant that is designed to more closely resemble the original bone itself. Often these implants comprise biodegradable polymeric compounds or parts made from such compounds. It is contemplated that bone tissue will grow back into the pores of the implant and will gradually replace the entire implant as the implant itself is gradually degraded in the in vivo environment. For obvious reasons then, such implants should be biocompatible and non-toxic.
Poly(propylene fumarate) (PPF) is one such polymer. Poly(propylene fumarate) (hereinafter "PPF") is an unsaturated linear polyester that degrades in the presence of water into propylene glycol and fumaric acid, degradation products that are easily cleared from the human body by normal metabolic processes. Because the fumarate double bonds in PPF are reactive and cross link at low temperatures, it has potential to be an effective in situ polymerizable biomaterial. The high mechanical strength of cured PPF matrices and their ability to be cross linked in situ makes them especially suitable for orthopedic application. Another advantage of cured PPF matrices is that they biodegrade into non-toxic propylene glycol and fumaric acid. On the basis of these unique properties, PPF has been formulated as bone cement, an orthopaedic scaffold for bone tissue regeneration, and a drug delivery system.
Several PPF-based formulation methods have been evaluated by varying such parameters as the molecular weight of PPF and the choice of cross linking reagents. For example, U.S. Pat. No. 5,733,951 discloses a composite mixture incorporating P(PF), a cross linking monomer (N-vinyl pyrrolidone), a porogen (sodium chloride), and a particulate phase (.beta.-tricalcium phosphate) that can be injected or inserted into skeletal defects of irregular shape or size.
To extend its application in biomedical science, PPF has been modified with polyethylene glycol (PEG), a highly flexible hydrophilic polyether, by transesterification. Incorporation of PEG into PPF decreases platelet adhesion on the material for cardiovascular application. Mechanical properties of a hydrogel made of poly(propylene fumarate-co-ethylene glycol) (P(PF-co-EG)) can be controlled by varying the ratio between hydrophilic PEG and hydrophobic PPF, as set out in concurrently filed application Ser. No. 09/550,372, entitled Poly(Propylene Fumarate) Cross Linked With Poly(Ethylene Glycol) incorporated herein by reference.
Despite advances in PPF technology, it is still desired to be able to modify PPF so as to increase its effectiveness for various bioactive purposes. For example, according to previous studies, the coupling of a cell adhesion peptide into PPF matrices for use as scaffold for tissue regeneration requires hydrophilic spacers. Because the hydrophilic spacers tend to reduce the desired mechanical properties of the resulting polymer, a method for modifying PPF to include one or more peptides without the need for hydrophilic spacers is desired.